Presently available serum markers of cardiac injury, such as the troponins, were developed as extensions of studies of these candidate proteins in basic cardiac physiology. In this proposal, we will test the following hypotheses: 1) That analysis of serum proteins from patients undergoing "planned myocardial infarction (PMI)," using unbiased proteomics technologies, will lead to the discovery of both novel markers of cardiac injury and novel serum response proteins which shed insight onto disease pathogenesis; 2) That novel markers and response proteins discovered in the setting of PMI will be valid in a heterogeneous population of myocardial infarction (MI) patients; and 3) That levels of novel markers and response proteins discovered in PMI will predict clinical outcomes in the heterogeneous MI population. Towards the goal of developing new cardiac markers, we first characterized serum from patients undergoing an alcohol septal ablation for hypertrophic cardiomyopathy, an in vivo model of human MI. In this population, we have identified peptide spectra and specific proteins that appear in the serum after myocardial injury. However, findings from this controlled patient subset must be validated in a heterogeneous patient cohort. Therefore, we will apply our preliminary data from the PMI group to the CLARITY-TIMI 28 trial, a large, double-blind, randomized clinical trial studying patients with acute ST elevation myocardial infarction (STEMI). In Specific Aim 1, we will characterize the recently identified peptide markers in the entire cohort of PMI patients. In Specific Aim 2, we will validate the novel markers in a diverse patient population of "normal myocardial infarction" in the TIMI trial. In Specific Aim 3, we will correlate elevations in novel protein markers and response proteins with outcomes in patients with acute MI in the TIMI trial.